Dendritic cells (DC) were shown to enhance the efficiency of HIV-1 infection of T cells through the binding of viral gp120 to a DC surface C-type lectin-like receptor, DC-SIGN, and subsequent delivery of the viral particles to T cells. The recruitment of DC-SIGN by HIV to facilitate the viral infection makes the receptor a potential new target for vaccines and anti-viral therapy. We have expressed several soluble forms of DC-SIGN and DC-SIGNR using a bacterial system followed by in vitro reconstitution. The refolded CRD, R8 and Ecto forms of DC-SIGN exist in solution as monomer, dimer and octamer, respectively, suggesting the function of the extracellular repeat region is to stabilize the oligomeric form of the receptor. Furthermore, the gp120 binding affinity of DC-SIGN increases as the receptor oligomerizes, suggesting that oligomerization plays an important role in the receptor recognition of gp120. We have also crystallized the R8 construct of DC-SIGNR. The structure was solved to 1.5 angstrom resolution. The structure shows that the CRD domain adopts a typical C-type lectin fold with both calcium and carbohydrate binding sites visible in the electron densities. The construct contains a single repeat and it assumes a helical conformation. Antibodies were raised against the recombinant DC-SIGN(R8) and one (II.1) exhibits near complete inhibition to the receptor/ gp120 binding both in solution and on the surface of immature dendritic cells, whereas the other display variable inhibition effects. In addition to the anti-DC-SIGN antibodies, two anti-gp120 antisera were also tested but were not able to block the gp120 binding to DC-SIGN. All constructs of the soluble receptor were subjected to crystallization screening experiments and the preliminary results show small crystals of the receptor can be obtained.